This invention pertains generally to systems and methods for detecting the yeast Candida auris (“C. auris”). More specifically, the invention is directed to the composition and use of yeast growth media that selectively supports or deters the growth of C. auris relative to other species of fungi.
C. auris has emerged as a novel organism causing infections in hospital settings. It is rapidly developing into a global threat. According to the Centers for Disease Control and Prevention (CDC): “Candida auris is an emerging fungus that presents a serious global health threat.” CDC, Candida auris, www.cdc.gov/fungal/diseases/candidiasis/Candida-auris.html. Within a period of only 7 years, the organism has caused healthcare-associated outbreaks in four continents. See, e.g., European Centre for Disease Prevention and Control, Candida auris in Healthcare Settings—Europe (Dec. 19, 2016), available at ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/Candida-in-healthcare-settings_19-Dec-2016.pdf; A. Chowdhary et al., Candida auris: a Rapidly Emerging Cause of Hospital-Acquired Multidrug-Resistant Fungal Infections Globally, 13(5) PLoS Pathogens e1006290 (May 18, 2017), available at journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006290; C. J. Clancy and M. N. Nguyen, Emergence of Candida auris: An International Call to Arms, 64 Clinical Infectious Diseases 141-143 (January 2017), available at doi.org/10.1093/cid/ciw696; M. Bougnoux et al., Healthcare-Associated Fungal Outbreaks: New and Uncommon Species, New Molecular Tools for Investigation and Prevention, 7:45 Antimicrobial Resistance & Infection Control (Mar. 27, 2018), available at doi.org/10.1186/s13756-018-0338-9. For example, major outbreaks were reported in Spain (33 bloodstream infections in a surgical ICU unit) and London (50 cases in a cardiothoracic center). S. Schelenz et al., First Hospital Outbreak of the Globally Emerging Candida auris In a European Hospital, 5:35 Antimicrobial Resistance & Infection Control (Oct. 19, 2016), available at doi.org/10.1186/s13756-016-0132-5. As of Jul. 31, 2018, there were more than 350 confirmed cases of C. auris infection in the US, with the majority of cases located in New York and New Jersey. CDC, Tracking Candida auris, www.cdc.gov/fungal/diseases/candidiasis/tracking-c-auris.html.
C. auris is prone to be spread in hospital settings and there are indications that it is becoming more widely established. In India, for example, C. auris at one point accounted for 5% of cases of candidemia acquired in intensive care units. A. Chakrabarti et al., Incidence, Characteristics and Outcome of ICU-Acquired Candidemia In India, 41 Intensive Care Medicine 285-295 (February 2015), available at link.springer.com/article/10.1007/s00134-014-3603-2. The species “has caused outbreaks in healthcare settings.” CDC, Candida auris, www.cdc.gov/fungal/diseases/candidiasis/Candida-auris.html.
C. auris infections are dangerous and difficult to treat. C. auris has the potential to be multi-drug resistant—isolates have been detected that are resistant to all major classes of antifungal agents. Thus, it is difficult to treat a C. auris infection. CDC, Candida auris, www.cdc.gov/fungal/diseases/candidiasis/Candida-auris.html. Invasive infections with C. auris currently carry a high mortality (30-60%), even if receiving treatment. See, e.g., CDC, Fact Sheet, www.cdc.gov/fungal/diseases/candidiasis/c-auris-drug-resistant.html (“More than 1 in 3 patients with invasive C. auris infection . . . die.”); S. E. Morales-López et al., Invasive Infections with Multidrug-Resistant Yeast Candida auris, Colombia, 23 Emerging Infectious Diseases 162-164 (January 2017), available at. dx.doi.org/10.3201/eid2301.161497; C. J. Clancy and M. H. Nguyen, Emergence of Candida auris: An International Call to Arms, 64 Clinical Infectious Diseases 141-143 (January 2017), available at doi.org/10.1093/cid/ciw696; S. R. Lockhart et al., Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses, 64 Clinical Infectious Diseases 134-140 (January 2017), available at doi.org/10.1093/cid/ciw691.
Because of the danger posed by C. auris, early detection is important. See, e.g., CDC, Candida auris,www.cdc.gov/fungal/diseases/candidiasis/Candida-auris.html (“it is important to quickly identify C. auris in a hospitalized patient so that healthcare facilities can take special precautions to stop its spread”); European Centre for Disease Prevention and Control, Candida auris in Healthcare Settings—Europe (Dec. 19, 2016), available at ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/Candida-in-healthcare-settings_19-Dec-2016.pdf. The need for early detection in a patient or a hospital environment is even more urgent since C. auris can persist on moist or dry surfaces in a hospital environment for at least 7-30 days. C. Piedrahita et al., Environmental Surfaces in Healthcare Facilities are a Potential Source for Transmission of Candida auris and Other Candida Species, 38 Infection Control & Hospital Epidemiology 1107-1109 (September 2017), available at doi.org/10.1017/ice.2017.127; A. Abdolrasouli et al., In Vitro Efficacy of Disinfectants Utilised for Skin Decolonization and Environmental Decontamination During a Hospital Outbreak With Candida Auris, 60 Mycoses 758-763 (2017), available at doi.org/10.1111/myc.12699.
Unfortunately, C. auris is not easy to identify and is prone to misdiagnosis by conventional methods. CDC, Candida auris, cdc.gov/fungal/diseases/candidiasis/Candida-auris.html. The CDC note that C. auris “is difficult to identify with standard laboratory methods, and it can be misidentified in labs without specific technology.” Id. Indeed, traditional detection methods result in “common misidentifications based on the identification method used.” CDC, Recommendations for Identification of Candida auris, www.cdc.gov/fungal/diseases/candidiasis/recommendations.html; see also, S. Kathuria et al., Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization—Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method, 53 Journal of Microbiology 1823-1830 (June 2015), available at jcm.asm.org/content/53/6/1823.full.pdf+html; A. Chowdhary et al., Candida auris: a Rapidly Emerging Cause of Hospital-Acquired Multidrug-Resistant Fungal Infections Globally, 13(5) PLoS Pathogens e1006290 (May 18, 2017), available at journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006290.
The state-of-the-art yeast-detection systems either fail to adequately identify C. auris (because of common misidentifications) or they are expensive and cumbersome to use. They fail to timely identify the presence—and threat—of C. auris. The failings in the detection systems and the multi-drug-resistant nature of Candida auris threaten dangerous outbreaks of Candida auris infections. Currently, no simple detectable markers for the presence of C. auris are known. In the near future, PCR-based methods may be available to detect the presence of C. auris DNA quickly and accurately. However, this method does not allow the distinction between dead and viable (i.e., colony-forming) cells and does not provide the cells for further investigation, e.g. analysis of their drug resistance (which is important for therapy) or their genetic makeup.
Accordingly, there is a need for a means to accurately and timely identify viable C. auris and to isolate those cells for further study.